Acute
and chronic effects of opiates and dopamine on
yawning, penile erection and genital grooming
behaviors in male Wistar rats

Mahdi Torkamani Noughabi, Gholamhassan
Vaezi,

Hossein Abtahi Eivari, Vida Hojati

Department of Biology,
Science and Research Branch,

Islamic Azad University,
Tehran, Iran

Abstract

Yawning is a contagious event that occurs
alone or associated with stretching and/or
penile erection. The aims of the present study
were to compare acute and chronic effects of
opiates and dopamine on yawning, penile erection
and genital grooming behaviors in male Wistar
rat. Sixty four male rats were divided into
eight groups and received, normal saline
(control group), Apomorphine-HCl (Apo, 0.08 mg/
kg), haloperidol (Hal, 0.1 mg/kg), naloxone-HCl
(Nal, 1 mg/kg), morphine-HCl (Mor, 5 mg/kg), Apo
+Nal, Apo+Mor or Nal+Hal. After acute phase (day
1) and the chronic phase (day 14), rats were
observed for the entire duration of the
experiment (60 min) at 10-min intervals in order
to count penile erection, yawning episodes and
the time spent on genital grooming. Previous
administration of morphine and naloxone
inhibited and increased the apomorphine effects,
respectively (P<0.05). Also, naloxone and
morphine were adverse and the previous acute
administration of haloperidol decreased the
naloxone effect; but previous chronic
administration of haloperidol increased the
naloxone effect. Our findings may explain the
opiates and dopamine roles on yawning, penile
erection and genital grooming behaviors in rat
as a model for human studies.

Introduction

Yawning is a phylogenetically old,
stereotyped event that happens under different
conditions alone or associated with stretching
and/or penile erection with a low frequency in
humans, in animals from reptiles to birds and
mammals. In rats and non-human primates yawning
is androgen-dependent and sexually dimorphic,
with more common in males than females. Yawning
occurs associated with increased
electroencephalographic activity of the cortex,
it has been also suggested that yawning is an
ancestral vestige survived through evolution
that occurs when attention is low and arousal
needs to be increased. Yawning is also
contagious, as it can be also evoked in humans
or non-human primates by a yawn produced by
another subject of the same species. This led to
suggest that yawning may be linked to empathy.
Neuropharmacological studies revealed that
various neurotransmitters and neuropeptides are
effective on yawning.

The best known are adrenocorticotropin,
alpha-melanocyte stimulating hormone (MSH) and
related peptides, acetylcholine, dopamine,
serotonin, excitatory amino acids, oxytocin,
gamma-peptides. Some of these interact at the
level o the paraventricular nucleus (PVN) of the
hypothalamus in the control of this behavioral
response. Dopamine is one of the most studied
neurotransmitters involved in the control of
penile erection and sexual behavior.
Accordingly, dopamine receptor agonists increase
penile erection and facilitate copulatory
behavior in rodents and also in other mammals
including non-human primates. On the other hand,
opiate interactions with both dopaminergic and
cholinergic systems have been demonstrated. A
close association between opiate receptors and
dopaminergic cell bodies and nerve endings in
the substantia nigra and striatum were also
reported. Therefore, the aims of the present
study were to compare acute and chronic effects
of opiates and dopamine drugs on yawning, penile
erection and genital grooming behaviors in male
Wistar rat. In view of interaction between
opiates and dopaminergic, the current study
aimed to investigate whether the yawning is
associated with genital grooming and penile
erection, and quantify these responses and
possible involved pharmacological mechanisms of
action amino butyric acid (GABA) and opioid

Discussion

Acute and chronic effects of opioids and
dopamine on yawning, penile erection and genital
grooming behaviors in male Wistar rat were
investigated in the present study. We found that
previous administration of morphine and naloxone
inhibits and increases the apomorphine effects,
respectively. Also, naloxone and morphine were
adverse and the previous acute administration of
haloperidol decreased the naloxone effect; but
previous chronic administration of haloperidol
increased the naloxone effect. It has been
reported that different agents such as several
neurotransmitters and peptidergic hormones
induce concomitant yawning, penile erection and
genital grooming.

The involvement of the dopaminergic system
in the induction of yawning and genital grooming
becomes evident through the administration of
small doses of apomorphine, a direct DA receptor
agonist, with marked affinity for DA D2 like
(D2/D3/D4) receptors. Furthermore, many
dopaminergic antagonists such as haloperidol
have been shown to be effective in inhibiting
these behaviors. In the present study,
apomorphine-induced yawning was inhibited in a
naloxone sensitive manner by morphine.

Although the nigrostriatal pathway has been
shown to be regulated by mu- and delta-opioid
receptors in the striatum and the substantia
nigra [24], such a mechanism is unlikely
to explain the present results since morphine in
a similar dose range also inhibited dopamine
receptor-mediated yawning. Morphine is able to
inhibit the release of acetylcholine in the
central nervous system in a naloxone-sensitive
manner and this can be explained in our findings
that morphine was able to inhibit the yawning
induced by the direct acting dopamine receptor
agonist, as well as that induced by
apomorphine.

The most likely explanation of the present
findings is that morphine inhibits yawning
induced by dopamine agonists and drugs acting at
an opioid site downstream from the dopamine
receptors. The weak but dose-dependent induction
of yawning by naloxone suggests that endogenous
opioids may mediate a tonic inhibitory effect on
yawning behavior. In fact, morphine reduced
drug-induced yawning, an effect which is
probably due to sedative side effects. It can be
concluded that the naloxone-androgen interaction
is not mediated via an opiate receptor or, if it
is, then it is a subtype of opiate receptor for
which morphine is not sufficiently selective.
The best known central neurotransmitters and
neuropeptides include serotonin, dopamine,
oxytocin, excitatory amino acids, NO,
adrenocorticotropin, MSH, and opioid peptides
control penile erection by acting in several
brain areas. It seems the PVN have a central
role and NO and oxytocin to be main players in
the mediation of the effects. NO seems to be
involved in the expression of opioid
antinociception, tolerance and dependence, so
between opioids and NO have been shown
interactions. In normal rats, morphine and
haloperidol blocked apomorphine-induced penile
erections whereas naloxone enhanced the
response. Since there is no evidence to suggest
otherwise, it is possible that the inhibition of
apomorphine-induced yawning, penile erections
and genital grooming in normal rats by morphine
as an opioid receptor agonist in acute and
chronic phase is due to direct interaction
between dopamine and opiate receptors.
Haloperidol at the chronic dose have an
enhancing effect on penile erection compared to
acute dose.

The enhancing effect may be explicable in
terms of postsynaptic blockade of dopamine
receptors by haloperidol there by preventing
inhibition by dopamine on the cholinergic
neurons. We found significant higher yawning in
response to morphine administration, higher
penile erection in response to Hal+Nal, morphine
and haloperidol administration and higher
genital grooming in response to Hal+Nal
consumption in chronic against acute
administration. Other changes in response to
other treatments were also found but they were
not statistically significant. No studies were
existed about the comparison of acute and
chronic effects of opiates and dopamine on these
behaviors. Therefore, the possible underlying
mechanism cannot be discussed. However, central
and possible peripheral actions of opiates on
their receptors and differences in time of
actions may be the possible reason. These need
future clarification, in further studies.

Conclusion

Acute and chronic adminstriation of
morphine, an opioid receptor agonist, reduced
almost completely penile erection, yawning and
genital grooming induced by apomorphine. So
there is interaction between dopamine and opiate
receptors. Injecting morphine in chronic phase
only enhances number of yawning. These results
may be explained by the ability of opioid
receptor agonists to markedly decrease oxytocin
neurotransmission at central and posterior
pituitary level. Dopamine in turn increases
central oxytocinergic neurotransmission, leading
to penile erection and yawning, as already
suggested for apomorphine and other dopamine
receptor agonists. Compounds enhancing yawning
would probably increase the penile erection and
genital grooming time behaviors in rat.